SUMMARY ? Yale ADRC Neuropathology Core The neuropathological assessment of brains provides a critical resource and asset for disease-oriented neuroscience by connecting clinical, biomarker-based, genetic and neuroimaging observations to pathogenic tissue-based changes. Alzheimer?s Disease (AD) research was enhanced by thorough neuropathological studies uncovering closely inter-related histopathological features with other defined neurodegenerative diseases and/or co-morbidities such as cerebrovascular disease and hippocampal sclerosis. Precise postmortem diagnosis is therefore critical for validating candidate antemortem biomarkers and imaging characteristics. The Yale ADRC Neuropathology Core has been designed to enhance research within the Yale ADRC and to promote tissue- based Alzheimer Disease research throughout the neurodegenerative disease research community. The biobanking of AD brains will be supplemented by the parallel collection of skin or dura derived fibroblasts from deceased individuals, which will be reprogrammed to induced pluripotent stem cells (IPSC). This approach leads to uniquely paired samples that allow the directed investigation of neurodegenerative disease processes in frozen/fixed brain samples while also providing a cell culture model of the same individual. Further, Yale is home to a large aged rhesus colony due to decades of pre-eminence of non-human primate (NHP) neuroscience. The incorporation of NHP brains the for assessment of age-related neurodegeneration in rhesus macaque will allow correlation of AD pathology and imaging across species, and it will provide high quality tissue samples for high resolution ultrastructure due to due to a well-controlled, minimal postmortem interval. The Neuropathology Core will also closely interact with other Cores of the Yale ADRC. The overarching goal of this application is to develop and establish a highly contemporary biobank, which merges traditional biobanking approaches with advancements in stem cell technology for the analysis of Alzheimer?s Disease, and also offers access to well-studied aged NHP brain tissue. Successful completion of these goals will have a major impact on the overall success of the Yale ADRC.